29th European Congress of Pathology (ECP 2017) … · Department of Surgical Pathology Aichi...

The Paris System for

Reporting Urinary Cytology:

The Concept and

Management

Toyonori Tsuzuki MD, PhDProfessor and Chair

Department of Surgical Pathology

Aichi Medical University Hospital

Tuesday, September 5, 2017

29th European Congress of Pathology (ECP 2017)

Amsterdam RAI.

The author has no conflict of interest to disclose

with respect to this presentation.

The 29th European Congress of

Pathology

Presenter: Toyonori Tsuzuki

Conflict of Interest (COI)



Outline of the presentation

• Why to standardize, why Paris?

• What is the guiding principle?

• What are diagnostic categories?

• What are the criteria?



Evolution of the Classification

Cancer Cytopathol. 2013 ;121:9-14Department of Surgical Pathology


• Reproducibility

• Improvement of communication

• Atypical cells

– Wide intraobserver variability

• Nationally rates of atypical vary among

institutions

– Range from 2% to 30%

Why standardize reporting of

urinary cytology?



Where did we start?

• 18th International Congress of Cytology, Paris, May, 2013

– Outline of the Paris System for Reporting Urinary

Cytopathology

– Ultimate goal – detection of high grade urothelial carcinoma

(HGUC)

• Numerous face-to-face meetings among 49 members, 28 from 10

countries including USA, Canada, France, Italy, Japan, Korea,

Luxembourg, Slovenia, Switzerland, and the UK.

Follow up schema by NCCN

Department of Surgical Pathology, Aichi Medical University Hospital

What is high grade urothelial

carcinoma (HGUC)?

• Life threatened cancer

• Need definitive therapies

• Need strict follow up

• Including urothelial carcinoma in situ

(CIS) and invasive urothelial carcinoma

(with divergent differentiation)

Department of Surgical PathologyAichi Medical University Hospital

Normal Urothelium

Hyperplasia Dysplasia

Low Grade Carcinoma High Grade Carcinoma Carcinoma in situ

Invasive Carcinoma

Papillary Pathway

80%

Non-Papillary Pathway

20%

9p-, 9q-

p16

Genetically Stable

FGFR3 (~85%)

Genetically Unstable

p53 (~60%)<10%

Recurrence Recurrence

RAS (?)

The Paris System

Chapters in the Book

I. Adequacy

II. Negative for High Grade Urothelial Carcinoma

III. Atypical Urothelial Cells

IV. Suspicious for High Grade Urothelial Carcinoma

V. High Grade Urothelial Carcinoma

VI. Low Grade Urothelial Neoplasm

VII. Other malignancies, both primary and secondary

VIII.Ancillary Studies

IX. Clinical management

X. Preparatory techniques relative to Urinary Tract samples



NEW paradigm

• It is all about High Grade Urothelial Carcinoma

• Negative for High Grade Urothelial Carcinoma

• AUC SHGUC HGUC

• LGUN – Low Grade Urothelial Neoplasm

Quality and Quantity Quantity



Adequacy



Adequacy

• Most of cytology systems require

minimum cell number.

• Minimum requirement for voided urine is

needed.

• What is “unsatisfactory” in voided urine?

• Which is better urine volume or cell

number?Department of Surgical Pathology


Evaluation of adequacy

Cancer Cytopathol 2016 ;124:174-80Department of Surgical Pathology


Evaluation of adequacy

(Malignant and suspicious cases)

Cancer Cytopathol 2016 ;124:174-80Department of Surgical Pathology


TPS requires ”30ml”,

at least.

Adequacy



Negative for HGUC

• Negative for High Grade Urothelial Carcinoma

– This diagnostic category will include cases where “low

grade urothelial carcinoma can not be excluded”

• If there is a cause for “atypia” i.e. urolithiasis,

treatment related changes etc. – it is negative!

Department of Surgical PathologyAichi Medical University

Various conditions:

Negative for HGUC

• Benign urothelial and squamous cells

• Reactive urothelial cells

• Polyoma Viral Cytopathic Effect: Decoy cells

• Benign Urothelial Tissue Fragments (BUTF)

• Post-therapy effect

• Changes associated with lithsiasis


What is your diagnosis?

Decoy cells!


Clinical history

• Patient: 50 years, Male

• The patient received chemotherapy for

malignant lymphoma.

• During his chemotherapy, microhematuria

was pointed out.

• A urine cytology test were performed


Are decoy cells

diagnosed correctly?

• BK virus infection in urinary tract is well-known in immunocompromised patients.

• Decoy cell is BK virus infected epithelial cell.

• TPS recommend to diagnose decoy cell as negative, not atypical.

• However, decoy cells might be diagnosed as “HGUC” in some case .


Which are decoy cells?

Decoy HGUCDepartment of Surgical PathologyAichi Medical University

Are decoy cells diagnosed

correctly?

Department of Surgical PathologyAichi Medical UniversityAllison DB, et al. Cancer Cytopathol 2016 ;124:436-42

• N/C ratio

• Hyperchromasia

• Plumped chromatin

• Nuclear membrane contour

• Size DOESN’T matter!

The Item of Morphological

Criteria in TPS


How to estimate N/C ratio


How to

estimate ?

N/C ratio =b/a

b

aa

b

ba

ab

a bDepartment of Surgical PathologyAichi Medical University

Do you

always

calculate?

Do we estimate correctly?

Department of Surgical PathologyAichi Medical UniversityCancer Cytopathol. 2016;124:669-77.

Cytopathologists and

cytothechnologist are aggressive!

Department of Surgical PathologyAichi Medical UniversityCancer Cytopathol. 2016;124:669-77.

• N/C ratio of 0.5 - 0.7

• Nuclear hyperchromasia, mild -

moderate

• Irregular granular chromatin

• Irregular nuclear membranes:

shapes and thickness

• Degenerated cells of uncertain atypia

The criteria of AUC


• N/C ratio of at least 0.7

• Marked hyperchromasia

• Markedly clumped chromatin

• Deformed nuclear membranes

• Cells of HGUC but only 5-10 of them

• Size DOESN’T matter!

The criteria of SHGUC


• N/C ratio at least 0.7

• Very hyperchromatic nuclei

• Grossly clumped chromatin

• Irregular nuclear contour

• Eccentric nuclei

• At least 10 cells

The criteria of HGUC


Hyperchromasia, Clumped chromatin, Deformed nuclear membranes

Size DOESN’T matter!


Mitosis and Apoptosis are helpful,

BUT do not trust!

Department of Surgical PathologyAichi Medical UniversityCancer Cytopathol. 2016;124:546-51

Low Grade Urothelial Neoplasm – LGUN

Eva M. Wojcik, Tatjana Antic, Ashish Chandra, Michael B. Cohen, Zulfia McCroskey,

Jae Y. Ro, and Taizo Shiraish

• LGUN - combined cytologic term for low grade papillary

urothelial neoplasms (LGPUN) (which include urothelial

papilloma, PUNLMP and LGPUC) and flat, low grade

intraurothelial neoplasia

Urothelial Papilloma PUNLMP Low Grade UC

Fibroblast Growth Factor Receptor 3 (FGFR3)

Why we avoid LGUC

• Almost impossible to diagnose without a

mini-biopsy with fibrovascular core

• Cytologically normal nuclei

• Is it truly a carcinoma?

• More common than HGUC

• BUT, not life threatening


Negative for HGUC, NOT LGUN

Summary

• The aim of TPS is standardization of criteria

and reporting.

• The main focus of TPS is detecting HGUC.

• Adequacy is important.

• Pitfall

– Decoy cell and other causes

• The presence of fibrovascular core is required

to diagnose LGUN.


Question ?


29th European Congress of Pathology (ECP 2017) … · Department of Surgical Pathology Aichi...

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